{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:35:03Z","timestamp":1778636103457,"version":"3.51.4"},"reference-count":60,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T00:00:00Z","timestamp":1745712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Hydrophobic ion pairing is a technique for reducing the hydrophilicity of charged molecules (drugs) by pairing them with oppositely charged hydrophobic counterions. This method is used to control the solubility of charged molecules in a solvent and is of particular importance in drug delivery. Methods: Dissipative particle dynamics simulations were performed to provide a microscopic understanding of hydrophobic ion pairing in polymyxin B (PMB) and oleate (OA) ions. Solvents and ions were explicitly included in the simulations. Results: We investigated the effects of relative concentrations of PMB and OA (the charge ratio), solvent philicity, and the concentrations of PMB and OA at a fixed composition on the structural stability and the hydrophobicity of the ion paired cluster, as well as the kinetics of assembly. The maximum hydrophobicity belongs to PMB:OA charge ratio 1:1. The clustering efficiency in mixed ethanol\u2013water solutions decreases with the increasing ethanol content of water. The dynamics of PMB\/OA exchange between hydrophobic cluster and the surrounding solution reveal two distinct relaxation processes, whose relaxation times differ by two orders of magnitude. Conclusions: The hydrophobicity of the cluster is controlled by the charge ratio. The core of the ion paired cluster acts as the primary barrier and its surface layer acts as the secondary barrier against alcohol permeation into it. The exchange of surface PMB\/OA ions with the surrounding is a much faster dynamic process than the establishment of equilibrium between the PMB\/OA ions in the cluster and the solution. The time scale for the slower process provides useful information on the rate of drug release from the hydrophobic ion paired complex.<\/jats:p>","DOI":"10.3390\/pharmaceutics17050574","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:28:11Z","timestamp":1746174491000},"page":"574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hydrophobic Ion Pairing of Polymyxin B with Oleic Acid: A Dissipative Particle Dynamics Simulation Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3570-0870","authenticated-orcid":false,"given":"Nargess","family":"Mehdipour","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Sciences, Persian Gulf University, Boushehr 75168, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sima","family":"Kiani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, Persian Gulf University, Boushehr 75168, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein","family":"Eslami","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, Persian Gulf University, Boushehr 75168, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cristofoli, M., Kung, C.-P., Hadgraft, J., Lane, M.E., and Sil, B.C. 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